Abstract 1305P
Background
Results from the first interim analysis (IA) from ALTA-1L (NCT02737501) showed that BRG has superior efficacy and tolerability with improved HRQoL vs CRZ in patients (pts) with ALK inhibitor–naive ALK+ NSCLC. Specifically, BRG delayed time to deterioration (TTD) and prolonged duration of improvement in global health status/quality of life (GHS/QoL), functional and symptom subscales. Here we report results from the second IA.
Methods
Pts with ALK+ NSCLC were randomized 1:1 to BRG or CRZ as first-line ALK inhibitor therapy. TTD (median time to deterioration, mo) in functional and symptom subscales of EORTC QLQ-C30 were analyzed in the ITT-PRO population (n=131 for each group). Subgroup analyses by baseline brain metastases and prior chemotherapy were conducted, and correlation of best response and TTD in HRQoL was evaluated among BRG pts.
Results
In addition to GHS/QoL (log-rank P=0.0485), BRG significantly delayed TTD versus CRZ for emotional and social functioning, as well as fatigue and GI-related symptoms (nausea and vomiting, appetite loss, and constipation; Table). Among pts with baseline brain metastases (n=38 for each group), BRG significantly delayed TTD for GHS/QoL (median: 16.6 vs 4.7 mo, hazard ratio [HR; 95% CI]: 0.54 [0.29, 1.00]; log-rank P=0.04); BRG also showed numeric improvement vs CRZ in other subgroups (no brain metastases, with/without prior chemotherapy). Among BRG pts, responders (n=100) vs nonresponders (n=31) had longer TTD in GHS/QoL (median: not estimable [NE] vs 7.7 mo, HR [95% CI]: 0.53 [0.28, 1.02]). Table: 1305P
TTD in EORTC QLQ-C30 scores, ITT-PRO population
| Median TTD, mo | HR 95% CI | ||
| BRG n=131 | CRZ n=131 | ||
| GHS/QoL | 26.7 | 8.3 | 0.70 0.49, 1.00 |
| Functioning | |||
| Physical | NE | 10.3 | 0.67 0.47, 0.97 |
| Role | 10.2 | 6.5 | 0.84 0.61, 1.17 |
| Emotional | NE | 10.1 | 0.56 0.38, 0.81 |
| Cognitive | 9.3 | 4.5 | 0.75 0.54, 1.02 |
| Social | 27.7 | 4.8 | 0.59 0.42, 0.85 |
| Symptoms | |||
| Fatigue | 15.6 | 4.8 | 0.67 0.48, 0.93 |
| Nausea and vomiting | 12.0 | 2.8 | 0.55 0.40, 0.76 |
| Pain | 12.1 | 8.1 | 0.82 0.59, 1.15 |
| Dyspnea | 28.6 | 16.8 | 0.98 0.67, 1.43 |
| Insomnia | NE | 22.1 | 0.91 0.61, 1.35 |
| Appetite loss | NE | 9.2 | 0.62 0.43, 0.90 |
| Constipation | 12.0 | 2.8 | 0.52 0.38, 0.73 |
| Diarrhea | 2.1 | 2.8 | 1.00 0.75, 1.34 |
Conclusions
With longer follow-up, BRG significantly delayed TTD versus CRZ in multiple functional and symptom subscales, consistent with findings from the first IA. Results of subgroup analyses, particularly in the patients with baseline brain metastases, also showed improved HRQoL by BRG. Response to BRG was correlated with delayed TTD in GHS/QoL.
Clinical trial identification
NCT02737501 Release date: March 30, 2016.
Editorial acknowledgement
Professional medical writing assistance was provided by Lauren Gallagher, RPh, PhD, of Peloton Advantage, LLC, an OPEN Health company, Parsippany, NJ, and funded by Millennium Pharmaceuticals, Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.
Legal entity responsible for the study
ARIAD Pharmaceuticals, Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.
Funding
ARIAD Pharmaceuticals, Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.
Disclosure
M.R. Garcia Campelo: Honoraria (self): ARIAD, AstraZeneca, Roche, Pfizer, BMS, Boehringer Ingelheim; Advisory/Consultancy, Speaker Bureau/Expert testimony: ARIAD, AstraZeneca, Roche, Pfizer, BMS, Boehringer Ingelheim. Y. Zhu: Full/Part-time employment: Takeda. H.M. Lin: Full/Part-time employment: Takeda. M. Pérol: Honoraria (self): Roche, Genentech, Eli Lilly, Pfizer, Boehringer Ingelheim, Clovis Oncology, MSD, Bristol-Myers Squibb, Novartis, AstraZeneca, Takeda, Chugai, Amgen; Research grant/Funding (institution): Roche, AstraZeneca, Boehringer Ingelheim, Takeda, Chugai. M. Jahanzeb: Research grant/Funding (institution): Lilly, Boehringer Ingelheim, Callisto, Takeda; Speaker Bureau/Expert testimony: Novartis, Roche Genentech, Pfizer, Takeda, Puma, BMS, AstraZeneca, Merck. S. Popat: Research grant/Funding (institution): Boehringer Ingelheim, Epizyme, BMS, Clovis Oncology, Roche, Lilly, Takeda; Honoraria (self): Boehringer Ingelheim, AstraZeneca, Roche, Takeda, Chugai Pharma; Advisory/Consultancy: Boehringer Ingelheim, Roche, Novartis, Pfizer, AstraZeneca, BMS, MSD, Guardant Health, AbbVie; Travel/Accommodation/Expenses: Boehringer Ingelheim, BMS, Merck Sharp & Dohme. P. Zhang: Full/Part-time employment: Takeda. E. Goodman: Full/Part-time employment: Takeda. D.R. Camidge: Honoraria (self): AstraZeneca, Takeda, Arrys/Kyn, Genoptix, G1 Therapeutics [DSMB], Mersana Therapeutics, Roche/Genentech, Ignyta, Daiichi Sankyo [ILD adjudication committee], Hansoh SRC, Bio-Thera DSMB, Lycera, Revolution Med, Orion, Clovis, Celgene, Novartis; Research grant/Funding (institution): ARIAD/Takeda.